Rectal cancers—although they arise through the same early APC/KRAS/TP53 pathway—exhibit a distinctive final repertoire of alterations and proteomic hubs compared with proximal colon tumors: rectal primaries have been reported to show relatively higher TP53 and FBXW7 mutation frequencies, higher rates of TOPO1 expression and a distinct pattern of ERBB2 amplification/mutation and other targetable alterations that differ from both left and right colon in frequency and hotspot distribution [57,58,59,60,61]. This evidence concerns the gene KRAS and colonic neoplasm.